Cathepsin D and epidermal growth factor in human breast cyst fluid.

Cathespin D (Cath D) is a proteolytic enzyme secreted by human breast cancer cells with a growth promoting activity in vitro. In the present study, we measured Cath D and Epidermal Growth Factor/alpha Transforming Growth Factor (EGF/alpha-TGF) concentrations in the breast cyst fluid (BCF) of 43 patients with gross cystic disease of the breast. Both Cath D (median 2.45 pmoles mg-1 protein; range 0-4.84 vs 0.98 pmoles mg-1 protein; range 0-3.11) and EGF/alpha-TGF (28.71 ng mg-1 protein; range 7.05-50.63 vs 10.83 ng mg-1 protein; range 0.06-30.55) levels were higher in BCF of apocrine than flattened cysts (P less than 0.0005 and P less than 0.01, respectively). Premenopausal patients showed higher concentrations of Cath D (P less than 0.05) and EGF/alpha-TGF (P less than 0.05) than postmenopausal patients. A positive correlation was obtained between intracystic concentrations of Cath D and EGF/alpha-TGF (P less than 0.00001). The higher levels of Cath-D and EGF/alpha-TGF found in apocrine cysts could provide an explanation for the increased risk of subsequent breast cancer in women with this type of cyst

Phase II study of the combination carboplatin plus celecoxib in heavily pre-treated recurrent ovarian cancer patients

Cyclooxygenase-2 overexpression is associated with poor outcome and resistance to platinum-based chemotherapy in ovarian cancer. We evaluated the antitumor activity and safety of the combination carboplatin plus the COX-2 inhibitor celecoxib in recurrent heavily-treated OC patients

Role of minimally invasive surgery versus open approach in patients with early-stage uterine carcinosarcomas: a retrospective multicentric study

Objective: The aim of this retrospective study was to compare surgical and survival outcome in only patients with early-stage UCSs managed by laparotomic surgery (LPT) versus minimally invasive surgery (MIS). Methods: Data were retrospectively collected in four Italian different institutions. Inclusion criteria were UCS diagnosis confirmed by the definitive histological examination, and stage I or II according to the FIGO staging system. Results: Between August 2000 and March 2019, the data relative to 170 patients bearing UCSs were collected: of these, 95 were defined as early-stage disease (stage I-II) based on the histological report at the primary surgery, and thus were included in this study. Forty-four patients were managed by LPT, and 51 patients were managed by MIS. The operative time was lower in the MIS group versus the LPT group (p value 0.021); the median estimated blood loss was less in the MIS group compared to the median of LPT group (p value < 0.0001). The length of hospital stay days was shorter in the MIS patients (p value < 0.0001). Overall, there were eight (8.4%) post-operative complications; of these, seven were recorded in the LPT group versus one in the MIS group (p value 0.023). There was no difference in the disease-free survival (DFS) and overall survival (OS) between the two groups. Conclusion: There was no difference of oncologic outcome between the two approaches, in face of a more favourable peri-operative and post-operative profile in the MIS group

The GOODSTEP project: General Object-Oriented Database for Software Engineering Processes

The goal of the GOODSTEP project is to enhance and improve the functionality of a fully object-oriented database management system to yield a platform suited for applications such as software development environments (SDEs). The baseline of the project is the O2 database management system (DBMS). The O2 DBMS already includes many of the features regulated by SDEs. The project has identified enhancements to O2 in order to make it a real software engineering DBMS. These enhancements are essentially upgrades of the existing O2 functionality, and hence require relatively easy extensions to the O2 system. They have been developed in the early stages of the project and are now exploited and validated by a number of software engineering tools built on top of the enhanced O2 DBMS. To ease tool construction, the GOODSTEP platform encompasses tool generation capabilities which allow for generation of integrated graphical and textual tools from high-level specifications. In addition, the GOODSTEP platform provides a software process toolset which enables modeling, analysis and enaction of software processes and is also built on top of the extended O2 database. The GOODSTEP platform is to be validated using two CASE studies carried out to develop an airline application and a business application

Inhibitory effect of quercetin on OVCA 433 cells and presence of type II oestrogen binding sites in primary ovarian tumours and cultured cells.

We investigated the effect of the flavonoid quercetin (Q) on the proliferation of the ovarian cancer cell line OVCA 433. Growth experiments demonstrated that Q exerted a reversible dose-dependent inhibition of cell proliferation in the range of concentrations between 10 nM and 10 microM. Two other flavonoids tested, rutin and hesperidin, were ineffective in inhibiting cell growth. Cell cycle analysis showed that the growth inhibitory effect of Q was due to a blocking effect in the GO/G1 phase. Using a whole cell assay with (6.7-3H) oestradiol (3H-E2) as tracer we demonstrated that OVCA 433 cells contain type II oestrogen binding sites (type II EBS). Competition analysis showed that Q competed for 3H-E2 binding to type II EBS while both rutin and hesperidin did not. Appreciable amounts of type II EBS were also detected in seven primary ovarian tumours. Our results suggest that Q may regulate ovarian cancer cell growth through a mechanism involving a binding interaction with type II EBS. This mechanism could also be active in vivo since primary ovarian tumours contain type II EBS

Expression of cyclooxygenase-2 (COX-2) in tumour and stroma compartments in cervical cancer: clinical implications

This study aims at investigating the relationship between cyclooxygenase-2 expression in tumour vs stroma inflammatory compartment and its possible clinical role. The study included 99 stage IB-IV cervical cancer patients: immunostaining of tumour tissue sections was performed with rabbit antiserum against cyclooxygenase-2. CD3, CD4, CD8, CD25, Mast Cell Tryptase monoclonal antibodies were used to characterise stroma inflammatory cells in nine cervical tumours. An inverse relation was found between cyclooxygenase-2 levels (cyclooxygenase-2 IDV) of tumour vs stroma compartment (r=−0.44, P<0.0001). The percentage of cases showing high tumour/stromal cyclooxygenase-2 IDV ratio was significantly higher in patients who did not respond to treatment (93.3%) with respect to patients with partial (60.5%), and complete (43.7%) response (P= 0.009). Cases with a high tumour/stroma cyclooxygenase-2 IDV ratio had a shorter overall survival rate than cases with a low tumour/stroma cyclooxygenase-2 IDV (P<0.0001). In the multivariate analysis advanced stage and the status of tumour/stroma cyclooxygenase-2 IDV ratio retained an independent negative prognostic role. The proportion of CD3+, CD4+, and CD25+ cells was significantly lower in tumours with high tumour/stroma cyclooxygenase-2 IDV ratio, while a higher percentage of mast cells was detected in tumours showing high tumour/stroma cyclooxygenase-2 IDV ratio. Our study showed the usefulness of assessing cyclooxygenase-2 status both in tumour and stroma compartment in order to identify cervical cancer patients endowed with a very poor chance of response to neoadjuvant therapy and unfavourable prognosis

External beam radiotherapy boost versus surgical debulking followed by radiotherapy for the treatment of metastatic lymph nodes in cervical cancer: A systematic review and meta-analysis.

We aimed to assess disease-free survival (DFS), overall survival (OS) and treatment-related toxicity of two therapeutic strategies for treating bulky lymph nodes on imaging in patients with locally advanced cervical cancer (LACC): radiotherapy boost versus surgical debulking followed by radiotherapy. We performed a systematic review of studies published up to October 2023. We selected studies including patients with LACC treated by external beam radiotherapy (EBRT) boost or lymph node debulking followed by EBRT (with or without boost). We included two comparative (included in the meta-analysis) and nine non-comparative studies. The estimated 3-year recurrence rate was 28.2% (95%CI:18.3-38.0) in the EBRT group and 39.9% (95%CI:22.1-57.6) in the surgical debulking plus EBRT group. The estimated 3-year DFS was 71.8% and 60.1%, respectively (p = 0.19). The estimated 3-year death rate was 22.2% (95%CI:11.2-33.2) in the EBRT boost group and 31.9% (95%CI:23.3-40.5) in the surgical debulking plus EBRT group. The estimated 3-year OS was 77.8% and 68.1%, respectively (p = 0.04). No difference in lymph node recurrence between the two comparative studies (p = 0.36). The meta-analysis of the two comparative studies showed no DFS difference (p = 0.13) but better OS in the radiotherapy boost group (p = 0.006). The incidence of grade≥3 toxicities (ranging 0-50%) was not different between the two approaches in the two comparative studies (p = 0.31). No DFS and toxicity difference when comparing EBRT boost with surgical debulking of enlarged lymph nodes and EBRT in patients with cervical cancer was evident. Radiotherapy boost had better OS. Further investigation is required to better understand the prognostic role of surgical lymph node debulking in light of radiotherapy developments